The immediate aim of the proposed research is to extend our knowledge and the scope of systemic two-stage carcinogenesis. The ultimate purpose of the research is to enable application of standard analytical procedures to the separate stages of initiation and promotion in systemic carcinogenesis which have been so successfully applied in the past to skin carcinogenesis. The proposed experiments may be considered under 2 headings: (1) The search for new initiators (e.g., tritiated thymidine) and potential promoters (e.g., various hormones) applicable to two-stage systemic carcinogenesis; and (2) the testing of new methods for two-stage systemic carcinogenesis. The latter include (a) transplacental carcinogenesis, with the initiator administered to the pregnant mother, and the promoter to the offspring after birth, and (b) the adaptation of intrasplenic transplantation of endocrine organs, to be performed in relation to feedback mechanisms via the pituitary, and the combined action of DMBA and results of intrasplenic transplantation.